The objective is to study the organization of the functional unit of the liver, the hepatic acinus, specifically for two processes: a. Bile formation and b. Drug metabolism. The functional organization of the hepatic acinus will be studied within the context of liver cell heterogeneity as there is now morphological and functional evidence that hepatocytes of the varius acinar zones are different. For this purpose, two approaches are proposed: 1. To isolate liver cell subpopulations originating from different zones of the hepatic acinus and to study the transport of these solutes involved in bile formation by each sub-population and 2. To study the structural characteristics of hepatocytes of acinar zones 1 and 3 with special emphasis on those parameters influencing the probability of solute-membrane interaction at each zone. In addition, target zones of the effects of drugs known to modify bile secretion will be defined, initially by morphological criteria.